Peptides are polymers of amino acids. Amino acids are generally alpha-amino carboxylic acids, mostly with another functional group substituted at the alpha-carbon. Peptides can be synthesised by condensation of single types of, or mixtures of, amino acids.
Peptides which occur in nature differ greatly in molecular weight and properties but generally comprise polymers of varying numbers of around 20 naturally occurring, amino acid monomers. These are known as the `standard` aminoacids, are generally of L-chirality and form peptides which have a highly structured sequence.
Random peptides can be synthesised in the laboratory with relative ease, whereas peptides with specific structured sequences require more complex synthetic methods. If it is desired that a synthetic peptide should simply have a structure which is not statistically random, this may be accomplished by modification of the molar ratio of amino acids present in the reaction mixture during the course of the synthesis.
For more highly structured peptides particular care must be taken to ensure that the reaction proceeds in discrete steps and this requires the use of either reaction-blocking agents or the so-called solid-phase synthesis, which employs a macroscopic substrate upon which peptides are grown and from which excess reagents can be washed. The nature of the reaction mixture may then be modified between each elongation step so as to ensure that specific sequences are produced.
For the purposes of the present specification the term `pseudo-random` will be used to refer to both completely random peptides and to those in which no steps have been taken to inhibit or restrict peptide growth to single step elongation of the peptide chains so as to produce an ordered sequence of residues. These peptides, having far less structure than those found in nature, are known and have found applications as drug carriers or as reagents in immunological assay techniques.
Highly structured peptides, which have specific amino-acid sequences are known to engage in specific biochemical reactions. Examples of such peptides include hormones such as insulin and enzymes such as amylase, which have specific metabolic functions. Slight modification of the amino-acid sequence of these peptides can result in partial, if not complete, alteration of function.
It is known that certain highly structured peptides, which occur in nature, have an inhibitory or lytic activity when micro-organisms are exposed to them. Other peptides are known, such as certain snake-venom components, which exhibit similar activity towards the cells of higher plants or animals.
EP 510912 (Morinaga Milk) discloses antibacterial peptides which contain one or more of a specified set of amino acid sequences which are believed to be derived from the overall sequence of bovine lactoferrin and can be isolated by enzymic digestion of that protein. EP 510912 also relates to peptides which are produced by a method of synthesis, using an automated peptide synthesis technique generally following the method of Sheppard et al. (Journal of the Chemical Society Perkin I, p 538 1981) to produce specific peptides.
It is commonly supposed that the synthesis of moderately complex peptides by so-called `genetic engineering` routes is a relatively simple task. However, despite considerable advances in recent years, the synthesis of specific peptides of a particular sequence on an industrial scale remains expensive and has been restricted to comparatively few peptides such as particularly valuable compounds of pharmacological interest and to certain enzymes. Thus, while structurally highly specific antimicrobial peptides are known they are expensive and difficult to produce.
The toxicity of antibacterial substances is conveniently expressed in terms of `log-kills`, e.g. a substance which reduces the viable count of cells in culture by 99.9% is effective at three log-kills, whereas a substance which reduces the viable count by a factor of 1 000 000 is effective at six log kills. For many applications of antibacterial substances 3-5 log kills is considered excellent performance. For dental pathogens, 2 log kills is considered adequate performance.
As will be apparent, the effectiveness of a particular antibacterial substance will be determined in part by the environment in which the substance acts and by the concentration of the substance. It should be noted that, particularly in bacterial populations, some cells may be resistant to the substance and effectiveness may not reach 100% (infinite log kills) even at high concentrations, whilst at much lower concentrations 3-5 log kills can still be achieved. Moreover, toxicity is expected to vary from one species of bacterium to another.
From the above it can be seen that, while some effective antibacterial peptides are known, they can be expected to be expensive to produce in relatively large quantities.
Antibacterial effects have been observed with simple peptides. In EP 0149254 (New York State University: 1985), poly L-histidine (of average molecular weight around 10000) is shown to have an antibacterial and fungicidal effect. It is believed that this effect is due to the structural similarity of these molecules to the naturally occurring histidine-rich peptides found in the mouth of humans and old-world monkeys.
EP 0254419 discloses that polylysine, especially that produced by the bacterium Streptomyces albus subsp (Dep 3834 FRI) has an antiviral activity.
GB 1237918 discloses that tetrapeptides of the general formula R-L-prolyl-L-leucyl-L-glycinamide and salts thereof, wherein R is an amino acid selected from glycine, tyrosine, leucine, tryptophan, serine, 3-hydroxypicolinic acid, asparagine, phenylalanine, proline, glutamic acid, arginine and histidine, express an antibacterial effect against a range of bacteria.
In order for antibacterial compounds to be used in products such as household cleaning compositions and household hygiene compositions they must be available at low cost, in quantity, and be effective at high log kills against a range of bacteria while present at relatively low levels.